CD4⁺FOXP3⁺ T regulatory cells decrease and CD3⁺CD8⁺ T cells recruitment in TILs from melanoma metastases after...

Area of Science:

• Oncology
• Immunology
• Dermatology

Background:

• Electrochemotherapy (ECT) is a local treatment for unresectable melanoma metastases.
• ECT combines anti-neoplastic drugs with cancer cell electroporation.
• The immune-activating effects of ECT remain under investigation, though dendritic cell recruitment has been observed.

Purpose of the Study:

• To investigate the immediate and late effects of ECT on T cell subsets within ECT-treated melanoma lesions.
• To analyze changes in T cell populations before and after ECT treatment.

Main Methods:

• Biopsies from 10 melanoma patients were collected before ECT (t0), and at 1 day (d1) and 14 days (d14) post-treatment.
• Fluorescent immunohistochemistry was used to analyze T cell subsets (CD3+CD4+, CD3+CD8+, CD4+FOXP3+ Treg cells).
• Calreticulin translocation was assessed as a marker of immunogenic cell death.

Main Results:

• Before ECT, CD4+ T cells were abundant, while CD8+ T cells were less frequent. Regulatory T cells (Tregs) were present in the perilesional dermis and lesion.
• ECT significantly decreased the percentage of CD4+FOXP3+ Treg cells at d1 and d14 (p < 0.001).
• The frequency of CD3+CD8+ T cells significantly increased at d14 post-treatment (p < 0.001). Calreticulin translocation was observed in metastatic cells.

Conclusions:

• ECT induces a local immune response in melanoma metastases, characterized by reduced Tregs and increased cytotoxic CD8+ T cells.
• These findings suggest ECT can modulate the tumor microenvironment to favor an anti-tumor immune response.
• The results support the potential of combining ECT with immunotherapy for long-lasting systemic anti-melanoma immunity.